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  • BMJ Publishing Group  (1)
  • The American Association of Immunologists (AAI)  (1)
  • 2015-2019  (2)
  • 1
    Publication Date: 2018-10-10
    Description: Aberrant activation of the NLRP3 inflammasome contributes to the onset and progression of various inflammatory diseases, making it a highly desirable drug target. In this study, we screened a series of small compounds with anti-inflammatory activities and identified a novel NLRP3 inflammasome inhibitor, AI-44, a curcumin analogue that selectively inhibited signal 2 but not signal 1 of NLRP3 inflammasome activation. We demonstrated that AI-44 bound to peroxiredoxin 1 (PRDX1) and promoted the interaction of PRDX1 with pro–Caspase-1 (CASP1), which led to the suppression of association of pro-CASP1 and ASC. Consequently, the assembly of the NLRP3 inflammasome was interrupted, and the activation of CASP1 was inhibited. Knockdown of PRDX1 significantly abrogated the inhibitory effect of AI-44 on the NLRP3 inflammasome. Importantly, AI-44 alleviated LPS-induced endotoxemia in mice via suppressing NLRP3 inflammasome activation. Taken together, our work highlighted PRDX1 as a negative regulator of NLRP3 inflammasome activation and suggested AI-44 as a promising candidate compound for the treatment of sepsis or other NLRP3 inflammasome-driven diseases.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2018-02-09
    Description: Objective To identify modifiable factors associated with sessile serrated polyps (SSPs) and compare the association of these factors with conventional adenomas (ADs) and hyperplastic polyps (HPs). Design We used data from the Tennessee Colorectal Polyp Study, a colonoscopy-based case–control study. Included were 214 SSP cases, 1779 AD cases, 560 HP cases and 3851 polyp-free controls. Results Cigarette smoking was associated with increased risk for all polyps and was stronger for SSPs than for ADs (OR 1.74, 95% CI 1.16 to 2.62, for current vs never, p trend =0.008). Current regular use of non-steroidal anti-inflammatory drugs was associated with a 40% reduction in SSP risk in comparison with never users (OR 0.68, 95% CI 0.48 to 0.96, p trend =0.03), similar to the association with AD. Red meat intake was strongly associated with SSP risk (OR 2.59, 95% CI 1.41 to 4.74 for highest vs lowest intake, p trend 〈0.001) and the association with SSP was stronger than with AD (p trend =0.003). Obesity, folate intake, fibre intake and fat intake were not associated with SSP risk after adjustment for other factors. Exercise, alcohol use and calcium intake were not associated with risk for SSPs. Conclusions SSPs share some modifiable risk factors for ADs, some of which are more strongly associated with SSPs than ADs. Thus, preventive efforts to reduce risk for ADs may also be applicable to SSPs. Additionally, SSPs have some distinctive risk factors. Future studies should evaluate the preventive strategies for these factors. The findings from this study also contribute to an understanding of the aetiology and biology of SSPs.
    Print ISSN: 0017-5749
    Electronic ISSN: 1468-3288
    Topics: Medicine
    Published by BMJ Publishing Group
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